Real-Time Particle Size Distribution Evaluation during Fluid Bed Granulation

Abstract

Fluid bed granulation has extensively been used for several decades within the pharmaceutical industry to improve powder properties (i.e., flowability, compressibility, etc.) for downstream processes. During this 2-phased process (spraying and drying period), primary particles aggregate due to the addition of a binder liquid which results into the formation of granules. The granule size distribution (GSD) is of major importance to the final quality of the granulated product as an inappropriate GSD influences the density, flowability and dustiness of the end product. In this study, a particle size analyser (Parsum IPP 70; Gesellschaft für Partikel-, Strömungs- und Umweltmesstechnik, Chemnitz, Germany) was mounted into a laboratory scale top-spray fluid bed granulator. A design of experiments (DoE) was performed to study the influence of several process (inlet air temperature during spraying and drying) and formulation variables (HPMC and Tween 20 concentration) upon the GSD, continuously in-line measured and compared to off-line laser diffraction data. Next, the in-line collected granule size data were related to off-line-determined end granule properties (tapped density and Hausner ratio) using univariate, multivariate and multiway models. The in-line particle size analyser provided every 10 s information about the granulation process, which allowed a clarification and better understanding of the (in)significance of the studied DoE variables upon granulation. In addition, we were able to predict end granule properties based on in-line GSD data, which can be valuable during development and routine production. The results of this study demonstrate the beneficial use of a particle size analyser during granulation. The tool was sensitive to any particle size changes during granulation and aids to increase granulation process understanding. Due to the continuous and rapid GSD measurements, granulation efficiency and control might be improved.